Lyotropic Liquid Crystalline Materials for Assay Substrata Binding

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Solution Overview

Problem

Current methods for binding assay substrata fail to provide a stable and protective environment for biomolecules, leading to degradation and inaccurate measurements in biochemical assays, particularly in mass spectrometry techniques like MALDI and SELDI, due to denaturation of sensitive proteins and poor substrate binding.

Innovation Solution

The use of lyotropic liquid and liquid crystalline materials that stably bind to assay substrata, encapsulating biomolecules and protecting them from degradative enzymes and denaturing effects, while promoting robust substrate binding and reducing run-to-run variability and increasing signal-to-noise ratios.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional binding methods are used for assay substrata, then the assay can be performed, but the biomolecules are exposed to degradative enzymes and denaturing effects, leading to degradation and inaccurate measurements

Engineering Contradiction:
Improveintegrity of biomolecule measurementsVSAvoidexposure to degradative enzymes and denaturing effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs lyotropic liquid crystalline materials as intermediary substances that form a protective barrier between the biomolecules and the harmful assay environment. These materials bind to the substrata and create a stable, protective microenvironment that shields sensitive proteins and standards from degradative enzymes and denaturing effects, thereby maintaining biomolecule integrity during the assay process

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The lyotropic liquid crystalline materials create an inert, protective environment around the biomolecules on the substrata. This environment is chemically stable and resistant to degradation, effectively isolating the biomolecules from harmful external factors such as proteases, nucleases, and other denaturing conditions present in the assay system

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

2Measurement precision

If standards are added to biological fluids for calibration, then charge/mass ratio and intensity can be calibrated, but the standards are degraded by proteases, lysozyme, trypsin, nucleases and other compounds in the biological fluids

Engineering Contradiction:
Improvecalibration accuracy of charge/mass ratio and intensityVSAvoiddegradation of standards by degradative enzymes
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

The lyotropic liquid crystalline materials serve as protective intermediaries that bind the calibration standards to the substrata in a stable configuration. This protective binding prevents proteases, lysozyme, trypsin, nucleases and other degradative compounds in the biological fluids from accessing and degrading the standards, thereby preserving their integrity for accurate calibration measurements

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies the protective lyotropic liquid crystalline coating to the substrata beforehand, before adding the standards to biological fluids. This pre-established protective barrier cushions the standards against upcoming exposure to degradative enzymes, ensuring their survival and maintaining calibration accuracy throughout the assay process

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Measurement precision

If multiple standard molecules are used for better calibration, then calibration coverage is improved, but run-to-run variability of peak positions and intensities confounds the calibration

Engineering Contradiction:
Improvecalibration coverageVSAvoidconsistency of peak positions and intensities
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies lyotropic liquid crystalline materials with specific local properties optimized for binding and stabilizing multiple different standard molecules. Each standard molecule benefits from the localized protective environment created by the liquid crystalline coating, ensuring consistent binding and stable peak positions and intensities across multiple standards and runs

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The lyotropic liquid crystalline materials modify the physical and chemical parameters of the substrata surface, creating a uniform and stable binding environment. This parameter modification reduces variability in peak positions and intensities by ensuring consistent interaction conditions for all standard molecules across different runs

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If solid surfaces are used to concentrate dilute species, then quantification is improved, but delicate proteins such as receptors denature or flocculate

Engineering Contradiction:
Improveconcentration of dilute analytesVSAvoidconformational stability of membrane proteins
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The lyotropic liquid crystalline materials act as intermediary substances that mediate between the solid substrata and delicate membrane proteins. These materials bind to the substrata and provide a protective, biomimetic environment that maintains the natural conformation and functionality of membrane-associated proteins while still enabling effective concentration and detection of dilute analytes

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enhances the integrity and accuracy of biomolecule measurements by maintaining the stability of standards and capture compounds, reducing variability, and improving signal strength and reproducibility in mass spectrometry assays.

Implementation Method 1

encapsulating biomolecules and protecting them from degradative enzymes and denaturing effects

Methodology Applied
Scientific EffectEncapsulation:

Implementation Method 2

lyotropic liquid and liquid crystalline materials that stably bind to assay substrata

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

providing a stable, protective environment for the compounds and a robust means for deposition on the chip

Methodology Applied
Scientific EffectStable binding:

Implementation Method 4

providing a stable, protective environment for the compounds

Methodology Applied
Scientific EffectProtective environment:

Implementation Method 5

protecting them from degradative enzymes and denaturing effects

Methodology Applied
Scientific EffectPrevention of denaturation:

Data Source

PatentUS8728829B2Compositions for binding to assay substrata and methods of using
Publication Date: 2014.05.20 LYOTROPICS THERAPEUTICS INC
  • US8728829B2 patent drawing
  • US8728829B2 patent drawing
  • US8728829B2 patent drawing

AI summary

Compositions and methods for binding to assay substrata in a stable and protective manner, thereby enhancing assay performance, are provided. The compositions comprise lyotropic materials (for example, lyotropic liquid and/or liquid crystalline materials) and may contain macromolecular standards, markers or capture compounds. The compositions are capable of binding to assay substrata such as that of chips that are employed for MALDI and SELDI mass spectroscopy analyzes and plates that are used for ELISA type assays.